Friend MuLV is a broad-spectarum leukemogen which can induce erythroid, meyloid and lymphoid leukemias depending in part on he strain of mouse inoculated. Thus, Balb/c mice develop erythrolelkemia (incidence Greater than 90 percent, latency about 8o days), while C57BL/6 mice develop myeloid and lymphoid leukemias (incidence about 90 percent, latency greater than 200 days). This striking difference does not appear to be due to differences in F-MuLV replication. To identify mouse genes involved in determining the latency and type of leukemia induced by F-MuLV, we are studying the susceptibility of F1, first and second backcross mice, congenic strains, and recombinat-inbred strains of mice derived from Balb/c and C57BL/6. Preliminary results indicate that the C57BL/6 phenotype (late lymphoid and myeloid leukemias) is determined by 1 or 2 dominant genes which are distinct from previously identidied Friend virus resistance genes including H-2, Fv-1 and Fv-2. Attempts to map these new genes are underway. We are also studying whether the leukemias induced by F-MuLV are clonal, and if so what cell lineages are involved in the leukemic clone, and when in the natural history of the disease clonality arises. Two techniques are being used: (1) "Southern blotting utilizing an ecotropic-specific viral DNA probe, and (2) determination of pgk isoenzyme type of tumor vs. normal tissue in femal mice heterozygous for the X chromosome-coded pgk enzyme.